(Figure 3)
Drainage. Thoracentesis or paracentesis can be performed for
symptomatic patients especially when mechanical ventilation is needed.
However, drainage of large volumes of chyle can lead to fluid shifts,
malnutrition, and immunocompromise due to loss of lymphocytes and
immunoglobulins. In dwelling catheters can be a source for infection and
can lead to a persistent chylous leak.
Shunting. Peritoneovenous or pleuroperitoneal shunts to drain
chylous effusion or ascites have been utilized.[23, 24]
Peritoneovenous shunts drain chylous ascites from the abdomen into the
superior vena cava. Technical limitations include the size of the shunt
relative to size of infant. Shunts complications include shunt
occlusion, thrombosis, infection, disseminated intravascular
coagulopathy, and need for shunt revision.[25] Shunting rarely
provides a durable solution.
Pleurodesis. Obliteration of the potential space between the
parietal and visceral pleura using chemical or a combination of chemical
and mechanical pleurodesis has had some success in managing chylous
effusions.[26] The procedure can be performed via tube thoracostomy
or a thoracoscopic approach. Talc, povidone-iodine, and doxycycline are
some of the agents used for pleurodesis.[26-28]
Surgical ligation. In preparation for surgical exploration due to
chylous effusion or ascites, efforts to maximize finding the leak should
be considered. Cessation of medical therapies to limit chyle production
prior to intervention combined with pre-operative fat loading can prove
helpful. It is not uncommon for surgeons to allow a patient to not only
eat but encourage ingestion of a high fat diet to better identify the
location of the lymphatic leak. Techniques described include 1 g of
Sudan III dye mixed in 30 ml of milk given 6 hours preoperatively.[21,
29, 30] Intranodal, intradermal, or subcutaneous injection of
lipophilic dyes prior to exploration can be used to facilitate
visualization.[21] Thoracoscopic and laparoscopic approaches limit
pain and can improve visualization; conversion to an open exploration is
not perceived as a failure and is sometimes necessary for a thorough
assessment. Suture ligation of the leaking lymphatic branch, thoracic
duct, or cisterna chyli can be performed.[31] Fibrin glue and
hemostatic or vicryl mesh are variably applied as reinforcement.[29]
Lymphovenous anastomosis and lymphaticovenous bypass of the thoracic
duct for the treatment of chylous leak in CCLA offers these patients a
potential durable cure.[32, 33] Early results show that
lymphaticovenous bypass does not ameliorate patients suffering with
intestinal lymphangiectasia and protein losing enteropathy.[33]
Drain placement at the time of surgical intervention is considered to
manage any persistent lymphatic leak. The biggest risk of surgery is
continued chylous leak.
Endolymphatic techniques. Thoracic duct or lymphatic channel
embolization is a minimally invasive alternative to surgical ligation
and can be successfully performed.[34, 35] It has several advantages
over the surgical technique in being minimally invasive and image
guided, but it can be challenging especially in premature infants and
small children with small central ducts. Complete thoracic duct
embolization usually involves placing microcoils and glue (n-butyl
cyanoacrylate) into the thoracic duct. Selective embolization of the
lymphatic channel can also be performed with coils and glue or glue
alone. Selective embolization preserves thoracic duct flow which can be
advantageous especially in patients with elevated central venous
pressure. Lymphatic duct embolization has been successfully used in
children with chylous effusions secondary to iatrogenic injury to the
lymphatic duct.[35] Risks of lymphatic embolization include
nontarget embolization to the periphery such as the lungs and
stroke.[34]
In patients with neonatal chylothorax, Lipiodol®embolization and low-fat diet has recently been shown as effective
treatment strategy.[7] In neonates with multicompartment disorders
care should be taken not to occlude the central lymphatic ducts as this
can lead to adverse outcomes. More selective and conservative management
is favored in the neonatal population with diet and diuretics.
Decompression strategies such as surgical lymphovenous anastomosis have
been showing promise.
Nutritional management: Patients with high output lymphatic leak
are at risk for severe nutritional deficiencies including vitamin D
25-hydroxy, zinc, copper and essential fatty acids.[36] While NPO,
TPN with intralipids is necessary to prevent essential fatty acid
deficiency.
Genetic sequencing: Many primary lymphatic malformations are due
to sporadic somatic mutations in genes that regulate lymphangiogenesis.
Gene variants often involve the VEGFC/VEGFR3 and PI3K/AKT/mTOR pathways.
Additionally, some genetic syndromes are associated with abnormal
lymphatic development including Down, Turner, Noonan and
Cardiofaciocutaneous syndromes.[37] Identification of a genetic
variant has implications for patient screening and management as
potential therapeutic targets are discovered. With the identification of
PI3K/AKT/mTOR variants within certain vascular malformations, their
targeted inhibition is now the subject of several active clinical
trials.[38] Sirolimus, an mTOR inhibitor further described below,
has been utilized to improve function in patients with complex lymphatic
anomalies. RAS/MAPK pathway variants have also been identified in
complex lymphatic anomalies and represent a novel therapeutic target
with MEK pathway inhibitors like trametinib.[39] Use of trametinib
to treat symptomatic pediatric vascular anomalies currently is limited
to the setting of a clinical trial or for compassionate use in the
setting of a lesion with an identified RAS/MAPK pathway variant.
Geneticists and genetic counselors are an increasingly important member
of the multidisciplinary vascular anomalies team.
Sirolimus (Rapamune): mTOR inhibition has been increasingly
utilized to improve function in symptomatic vascular anomalies. The
mechanism of action is presumed to be the inhibition of an overactive
PI3K/AKT/mTOR pathway, decreasing inappropriate cell growth and
angiogenesis. Phase II trials have demonstrated efficacy of sirolimus in
vascular anomalies including complex lymphatic anomalies.[40]
Despite a paucity of data, sirolimus is used as a first-line
pharmacotherapy agent in symptomatic Gorham Stout, Kaposiform
lymphangiomatosis, and generalized lymphatic anomaly. Sirolimus’
efficacy in treating central conducting lymphatic anomaly is not known
and is utilized as a secondary agent for refractory lymphatic leak.
Although dosing practices vary, for use to treat pediatric vascular
anomalies, we commonly initiate sirolimus at 0.8
mg/m2/dose given twice daily by mouth and further
titrated to a serum trough level of 10-15 ng/ml.[40] Caution should
be taken to dose reduce sirolimus in the newborn and premature infant
with presumed immature drug clearance (consider starting dose of 0.2
mg/m2/dose given twice daily in the newborn or
premature infant).[41] Concurrent Pneumocystis jiroveci
pneumonia prophylaxis is recommended. Side effects include neutropenia,
mucositis, peripheral edema, hypertension, hypertriglyceridemia,
hypercholesterolemia, headache, and elevation of liver transaminases.